As part of a broad program concerning the total synthesis of biologically-active natural products and analogs not found in nature, we have initiated studies directed toward the synthesis of sesquiterpene alpha-methylene-gamma-lactones and cyclic biphenyls. The lactones are important targets for practical synthesis because members of this family display considerable biological activity as allergenic agents, growth inhibitors, antibacterial agents, and antitumor agents. The cyclic biphenyls such as steganacin and steganangin are known antileukemia and antitumor agents, while a unique new structural family, the alnusones, has not been tested for biological activity. We have shown the feasibility of a new strategy for alpha-methylene-gamma-lactone synthesis and will be working out optimum conditions while applying the method to the total synthesis of helenalin, confertin, and related natural products. New methods are proposed and, after preliminary studies on model systems, will be applied in the synthesis of ambrosin. The new methods involve organo-transition metal intermediates and controlled potential electrolysis, with unique selectivity compatible with the delicate functional groups in the natural products. We have prepared dimethyl alnusone using organo-nickel reagents and propose to prepare alnusone itself as well as alnusoxide and alnusonol. These organo-metal techniques and electro-oxidative phenol coupling will be applied to the synthesis of steganone, steganacin, and steganangin. Preliminary biological screening of intermediates and synthetic stereoisomers of the natural compounds will be done at Cornell, including toxicology on the more active compounds.